Triethylamine → Enzalutamide carboxylic acid

HRID 705416Notes

Reaction equation

HRID 705416 reaction equation
[C:1]([C:4]([NH:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[C:10]([F:17])[CH:9]=1)([CH3:6])[CH3:5])([OH:3])=O.[N:18]([C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[C:23]([C:29]([F:32])([F:31])[F:30])[CH:22]=1)=[C:19]=[S:20].C(N(CC)CC)C>CCO>[C:25]([C:24]1[CH:27]=[CH:28][C:21]([N:18]2[C:1](=[O:3])[C:4]([CH3:6])([CH3:5])[N:7]([C:8]3[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[C:10]([F:17])[CH:9]=3)[C:19]2=[S:20])=[CH:22][C:23]=1[C:29]([F:30])([F:31])[F:32])#[N:26]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 673955034-(2-Carboxypropan-2-ylamino)-2-fluorobenzoic acid

Product 1

HCID 46898522Enzalutamide carboxylic acidYield 2.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

4-(1-Carboxy-1-methyl-ethylamino)-2-fluoro-benzoic acid (241 mg, 1 mmol), 4-isothiocyanato-2-trifluoromethylbenzonitrile (342 mg, 1.5 mmol) and triethylamine (343 mg, 3.4 mmol) were mixed in EtOH (5 mL) and the solution was stirred for 10 days at room temperature. The reaction mixture was concentrated under reduced pressure, the residue was acidified with 1M aqueous HCl, and the product was extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product obtained was purified by column chromatography eluting with ethyl acetate to obtain 4-[3-(4-cyano-3-trifluoromethyl-phenyl)-5,5-dimethyl-4-oxo-2-thioxo-imidazolidin-1-yl]-2-fluoro-benzoic acid (10 mg) as an off white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionthe product was extracted with ethyl acetate
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product obtained
  6. customwas purified by column chromatography
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-53a62065c1ab4682a5a859b9df82a20c
Source dataset
uspto-grants-2015_11
Patent number
US09174943B2

Reaction notes

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